Radon Anomaly: A Possible Precursor of the 1978 Izu-Oshima-kinkai Earthquake.

Precursory changes in the radon concentration of groundwater were observed prior to the Izu-Oshima-kinkai earthquake (magnitude 7.0) 14 January 1978. The distance from the epicenter to a continuous radon-monitoring station at Nakaizu was about 25 kilometers. A sudden drop and a subsequent increase in the radon concentration recorded on 9 January 1978 were significant. The size of the spike-like change was about 15 percent. After the earthquake, a remarkable increase in the radon concentration occurred.

Hydrogen release: new indicator of fault activity.

The hydrogen concentration in soil gas has been measured in the area around the Yamasaki Fault, one of the active faults in southwestern Japan. Degassing of a significant amount of hydrogen (up to more than 3 percent by volume) has been observed for sites along the fault zone. The hydrogen concentration in soil gas at sites away from the fault zone was about 0.5 part per million, almost the same as that found in the atmosphere. The spatial distribution of sites with high hydrogen concentrations is quite systematic. A hypothesis on the production of hydrogen by fault movements is postulated.

"Helium spots": caused by a diapiric magma from the upper mantle.

"Helium spots," where a significant amount of helium is present in the soil [up to 350 parts per million with a high (3)He to (4)He ratio of (8.90 +/- 0.31) x 10(-6)], have been found along the fault zone formed by the 1966 Matsushiro swarm earthquakes. The formation of the "helium spots" and the occurrence of the earthquakes are interpreted as the results of a diapiric uprise of a magma approximately 1 kilometer in diameter.

Carbon dioxide degassing by advective flow from Usu volcano, Japan.

Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March 2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an increase in CO2 flux was detected on the summit caldera, from 120 (September 1998) to 340 metric tons per day (September 1999), followed by a sudden decrease to 39 metric tons per day in June 2000, 3 months after the eruption. The change in CO2 flux and seismic observations suggests that before the eruption, advective processes controlled gas migration toward the surface. The decrease in flux after the eruption at the summit caldera could be due to a rapid release of CO2 during the eruption from ascending dacitic dikes spreading away from the magma chamber beneath the caldera.

Plasma free triiodothyronine response to thyrotropin-releasing hormone to predict the remission of Graves' disease treated with antithyroid drugs.

The responses of both plasma TSH and free T3 (FT3) to TRH were examined in 31 patients with Graves' disease who were euthyroid after treatment with antithyroid drugs, 6 patients with primary hypothyroidism, and 14 control subjects. TSH was measured 0, 15, 30, 60, 90, and 120 min and FT3 was measured 0, 30, 60, 90, 120, 150, and 180 min after TRH injection (500 microgram, iv). The increment in FT3 above the basal level (delta FT3) in normal controls ranged from 1.2-3.7 pmol/L, with a mean +/- SD of 2.2 +/- 0.8 pmol/L. The mean (+/- SD) delta FT3 in patients with primary hypothyroidism was 0.3 +/- 0.2 pmol/L. After the TRH test, antithyroid drugs were stopped in patients with Graves' disease. Nine of 31 Graves' patients relapsed within 6 months after the TRH test. The other 22 patients with Graves' disease were followed while in remission during the observation period of up to 48 months. The mean (+/- SD) delta FT3 were significantly lower in 9 Graves' patients who relapsed than in those who achieved remission (0.5 +/- 0.3 vs. 2.6 +/- 1.1 pmol/L; P less than 0.01). Eight of 9 Graves' patients who relapsed showed lower delta FT3 values than the lowest value (1.1 pmol/L) in 22 Graves' patients in remission. Although the mean increment of TSH above the basal level (delta TSH) was also significantly different between the Graves' patients who relapsed and those in remission (1.4 vs. 12.3 mU/L; P less than 0.01), there was considerable overlap between the 2 groups. These findings suggest that delta FT3 reflects the endocrinological recovery of the pituitary-thyroid axis and is a beneficial indicator for the termination of antithyroid drugs in Graves' disease.

Correlation of plasma free thyroxine levels with insulin sensitivity and metabolic clearance rate of insulin in patients with hyperthyroid Graves' disease.

Insulin sensitivity, metabolic clearance rate of insulin (MCR-I) and basal posthepatic insulin delivery rate (BIDR) were investigated by means of euglycemic clamp technique in 8 normal subjects and 8 patients with hyperthyroid Graves' disease. The mean (+/- SD) steady-state glucose infusion rate (SSGIR) was lower in hyperthyroid Graves' patients than in normal subjects (228.9 +/- 57.0 vs. 290.9 +/- 49.4 mg/m2/min, p < 0.05). Both MCR-I and BIDR were higher in hyperthyroid Graves' patients than in normal subjects (1162.9 +/- 517.1 vs. 463.5 +/- 103.9 ml/m2/min, p < 0.005; 17.7 +/- 12.6 vs. 3.6 +/- 0.9 mU/m2/min, p < 0.01, respectively). Plasma free T4 levels showed a close correlation with MCR-I (r = 0.77, p < 0.05) and BIDR (r = 0.81, p < 0.05), respectively, in Graves' patients. These findings indicate that hyperthyroidism is characterized by not only a decrease in insulin sensitivity, but also an increase in basal insulin secretion and the metabolic clearance rate of insulin, which are correlated with plasma free T4 levels.

[Clinical epidemiology of autoimmune thyroid disorders--variation of natural history in patients with autoimmune thyroid disorders].

Clinical and epidemiological study for autoimmune thyroid disorders was performed in a rural community. Ninety-six of 1,686 subjects had asymptomatic autoimmune thyroiditis and were followed from 1979 to 1988. TRH loading test was carried out in 91 of 96 cases between 1983 and 1984. Each individual was classified into 4 subgroups. Five patients had normal levels of basal plasma TSH and had no increment of peak levels of plasma TSH (Grade G). Twenty-three had normal levels of both basal and peak plasma TSH (Grade I). The peak plasma TSH levels in 53 patients was high, but the basal was within the normal range (Grade II). Ten had high levels of both basal and peak plasma TSH (Grade III). One of the 5 Grade G cases developed overt Graves' disease in 1987 and another Grade III case suffered from goitrous Hashimoto's thyroiditis with primary hypothyroidism. Four of the ten Grade III cases and one Grade II case developed primary myxedema during the observation period. These results show that the natural history of asymptomatic autoimmune thyroiditis is variable and the prevention of overt autoimmune thyroid disorders is difficult.

[Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia].

Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia.

[Acute myelogenous leukemia transformed from myelodysplastic syndrome with tetraploid chromosome constitution].

A 57-year-old female presented with general fatigue. She had neither lymphadenopathy nor hepatosplenomegaly. Laboratory data revealed anemia and leukopenia (1,500/microliters) with a differential count of 4.5% leukemic cells. The myelogram revealed 34.4% leukemic cells, of which diameter ranged from 20 to 28 microns. The diagnosis was acute myelogenous leukemia (FAB: M2) with myelodysplasia. Cytogenetic analysis revealed that the leukemic cells had chromosome abnormalities involving both diploidy and tetraploidy with structural rearrangement. Structural rearrangement included del(5) (q22q33), del(15) (q22q24), and t(3; 12) (q25;p13). Small dose aclacinomycin-A treatment was effective in reducing the number of leukemic cells in bone marrow, and both anemia and leukocytopenia were improved.

[Clinical use of serum erythropoietin determination by the recombigen EPO RIA kit].

Serum erythropoietin (EPO) levels were determined by the recombigen EPO RIA kit (DPC) in normal subjects and patients with renal dysfunction, diabetes mellitus, hypothyroidism and a variety of hematological disorders. Mean (+/- SD) serum EPO levels were 18.6 +/- 5.6 mU/ml in 180 normal subjects and no sex difference was obtained. Serum EPO levels in older subjects were slightly greater than those in younger subjects. There was a negative correlation between serum EPO levels and Ht values in anemic patients with normal renal function, whereas serum EPO levels were within the normal range in anemic patients with renal disorders, suggesting that serum EPO levels were relatively low in patients with chronic renal failure. Serum EPO levels were rather increased in patients with diabetes mellitus and hypothyroidism. High serum EPO levels were obtained in patients with a variety of hematological disorders such as acute leukemia, multiple myeloma, myelodysplasia syndrome, aplastic anemia and pure red cell aplasia. In a patient with pure red cell aplasia treated with glucocorticoids, serum EPO levels were lowered before anemia was recovered and reticulocytes were increased. These findings indicate that measurement of serum EPO levels are useful for not only differential diagnosis of anemia but also clinical evaluation of the treatment.

[Adult type of idiopathic paroxysmal cold hemoglobinuria].

A 78-year-old female suffered from idiopathic paroxysmal cold hemoglobinuria (PCH). Her symptom occurred immediately after she worked outside in the cold early morning. This case is characterized by the eldest case with non-syphilitic PCH reported in Japan and by the most advanced anemia (Hb 4.2 g/dl) possibly due to prolonged hemolysis after cold exposure. Analysis of the serum revealed positive Donath-Landsteiner antibody of IgG type, which could react to hemolysis not only below 15 degrees C but also at 15-20 degrees C in vitro.

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Triphasic changes in thyroid function in a patient with primary hypothyroidism in the course of pregnancy and the early post-partum period.

We report a rare case of primary hypothyroidism in which thyroid function was changed from hypothyroidism to hyperthyroidism in the course of pregnancy and finally returned to hypothyroidism in the early post-partum period. She delivered an infant with neonatal Graves' thyrotoxicosis. Serum thyroid-stimulating antibodies (TSAb) and thyroid stimulating-blocking antibodies (TSBAb) coexisted in these patients. The triphasic changes in thyroid function may be explained by altered balance between TSAb and TSBAb in relation to pregnancy and delivery in the present case, although cellular immunity could be independently involved in atrophic changes in the postpartum period.

[Incidence of abnormal thyroid function in patients with low titers of thyroid microsomal antibodies].

The incidence of abnormal thyroid function related to autoimmune disorders was examined in a district of Shimane Prefecture in 1988. Thyroid microsomal antibodies (MCPA) in sera were measured in a general population of 1,646, including 678 males and 968 females, aged 57.8 +/- 14.8 (mean +/- SD) yr. MCPA titer was defined as high (less than 1:128), low (1:16, 1:32, 1:64) or negative (less than 1:16) according to the highest dilution of test serum capable of agglutinating gelatin particles coated with the appropriate antigen. Test of MCPA revealed high titers in 141 subjects (group A), low in 43 subjects (group B) and negative in 1,462 (group C). Twenty-four patients with overt thyroid disorders were found in groups A and B: five with Graves' disease, two with Hashimoto's thyroiditis and 15 with goiter in group A, and two with goiter in group B. In the remaining 119 subjects in group A and 41 subjects in group B, serum free T4 (FT4) and TSH levels were measured. According to abnormalities in the levels of serum FT4 and/or TSH, their thyroid function was divided into the following 3 subgroups: 1) hyperthyroid (FT4 greater than 2.0 ng/dl, TSH less than 0.4 mu U/ml), 2) latent hypothyroid (0.8 less than FT4 less than 2.0 ng/dl, TSH greater than 5.0 mu U/ml) and 3) hypothyroid (FT4 less than 0.8 ng/dl, TSH greater than 5.0 mu U/ml). The hyperthyroid group consisted of two patients in group A and one in group B. Ten latent hypothyroid patients were found in group A and two in group B. Hypothyroidism was found in four patients in group A. The incidence of abnormal thyroid function was not different between group A (16 out of 119, 13.4%) and group B (three out of 41, 7.3%). Graves' disease and primary myxedema were found in one patient each in group B; these patients had no subjective symptoms but showed low titers of MCPA. These findings suggest that not only high titers of MCPA but also low titers of MCPA are closely related to abnormal thyroid function.

[Effect of arotinolol on insulin secretion and insulin clearance rate in patients with Graves' disease].

Glucose-induced insulin secretion, 24-h urinary C-peptide (CPR) and euglycemic clamp were examined in five patients with hyperthyroid Graves' disease before and 2 weeks after treatment with arotinolol (20 mg/day, p.o.). Plasma glucose and insulin responses to oral administration of 75 g glucose were not changed by arotinolol treatment. 24-h urinary CPR and basal posthepatic insulin delivery rate (BPIDR) as an indicator of insulin secretion were significantly suppressed by arotinolol. Glucose infusion rate (GIR) as an indicator of insulin sensitivity and glucose clearance rate (GCR) were not influenced by arotinolol therapy. Insulin clearance rate (ICR) was significantly suppressed by arotinolol. These findings suggest that arotinolol inhibits insulin secretion by decreasing ICR but does not attenuate insulin release induced by glucose in hyperthyroid patients, and that insulin sensitivity and GCR are not affected by arotinolol.